Fig. 4.
R7 targeting requires only FNIII domains 7–9 in the LAR extracellular domain. (A) A schematic of the different LAR extracellular deletion constructs. Squares indicate FNIII domains and circles Ig domains. (B) Quantification of R7 targeting defects. In Larc12/Lar2127, elav-GAL4 mutants only 20% of R7 axons are correctly targeted. Pan-neuronal expression of the UAS-LAR extracellular deletion constructs rescues R7 targeting if they retain FNIII domains 789 (ΔIg123 73%, ΔFNIII123 69%, ΔFNIII456 81%, ΔIgΔFNIII1–6 75%, FL 83%). Constructs lacking FNIII789 do not rescue R7 targeting (ΔFNIII2–9 10%, ΔFNIII789 13%). (C and D) Horizontal sections of adult heads carrying glass-lacZ and stained with anti-β-galactosidase. Arrowheads indicate the terminal layers of R8 (blue) and R7 (red). (C) Larc12/Lar2127, elav-GAL4; UAS-LARΔFNIII789/+. (D) Larc12/Lar2127, elav-GAL4; UAS-LARΔIgΔFNIII1–6/+. (E) Distinct mechanisms of LAR signaling in Drosophila neurons. LAR (purple) may promote synapse growth as a catalytically active monomer with an unpaired wedge domain (W) that can dephosphorylate tyrosine-phosphorylated substrates (pY, red). The HSPG ligand Sdc acts in motor neurons to increase LAR activity by binding to its Ig domains (circle). Active zone morphogenesis requires competitive binding of the inhibitory HSPG ligand Dlp expressed in muscle cells to the Ig domains. Dlp inhibits LAR phosphatase activity, perhaps by inducing dimerization through insertion of the wedge domain of one monomer into the active site of the other. R7 targeting requires binding of an unknown ligand (L) to FNIII domains 7–9 (square), and an intact wedge domain. Dimerization mediated by the wedge domain may result in conformational changes that allow binding of a transmembrane ligand presented by the medulla target cells, or an intracellular adaptor protein (green). This scaffolding function of LAR might increase adhesion to target neurons through interactions with an intracellular protein network (yellow).